Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients

ABSTRACT Infections due to Mycobacterium abscessus are a major cause of mortality and morbidity in cystic fibrosis (CF) patients. Furthermore, M. abscessus has been suspected to be involved in person-to-person transmissions. In 2016, dominant global clonal complexes (DCCs) that occur worldwide among...

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Main Authors: Nils Wetzstein, Margo Diricks, Thomas A. Kohl, Thomas A. Wichelhaus, Sönke Andres, Laura Paulowski, Carsten Schwarz, Astrid Lewin, Jan Kehrmann, Barbara C. Kahl, Karl Dichtl, Christian Hügel, Olaf Eickmeier, Christina Smaczny, Annika Schmidt, Stefan Zimmermann, Lutz Nährlich, Sylvia Hafkemeyer, Stefan Niemann, Florian P. Maurer, Michael Hogardt
Format: Article
Language:English
Published: American Society for Microbiology 2022-08-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.01714-22
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author Nils Wetzstein
Margo Diricks
Thomas A. Kohl
Thomas A. Wichelhaus
Sönke Andres
Laura Paulowski
Carsten Schwarz
Astrid Lewin
Jan Kehrmann
Barbara C. Kahl
Karl Dichtl
Christian Hügel
Olaf Eickmeier
Christina Smaczny
Annika Schmidt
Stefan Zimmermann
Lutz Nährlich
Sylvia Hafkemeyer
Stefan Niemann
Florian P. Maurer
Michael Hogardt
author_facet Nils Wetzstein
Margo Diricks
Thomas A. Kohl
Thomas A. Wichelhaus
Sönke Andres
Laura Paulowski
Carsten Schwarz
Astrid Lewin
Jan Kehrmann
Barbara C. Kahl
Karl Dichtl
Christian Hügel
Olaf Eickmeier
Christina Smaczny
Annika Schmidt
Stefan Zimmermann
Lutz Nährlich
Sylvia Hafkemeyer
Stefan Niemann
Florian P. Maurer
Michael Hogardt
author_sort Nils Wetzstein
collection DOAJ
description ABSTRACT Infections due to Mycobacterium abscessus are a major cause of mortality and morbidity in cystic fibrosis (CF) patients. Furthermore, M. abscessus has been suspected to be involved in person-to-person transmissions. In 2016, dominant global clonal complexes (DCCs) that occur worldwide among CF patients have been described. To elucidate the epidemiological situation of M. abscessus among CF patients in Germany and to put these data into a global context, we performed whole-genome sequencing of a set of 154 M. abscessus isolates from 123 German patients treated in 14 CF centers. We used MTBseq pipeline to identify clusters of closely related isolates and correlate those with global findings. Genotypic drug susceptibility for macrolides and aminoglycosides was assessed by characterization of the erm(41), rrl, and rrs genes. By this approach, we could identify representatives of all major DCCs (Absc 1, Absc 2, and Mass 1) in our cohort. Intrapersonal isolates showed higher genetic relatedness than interpersonal isolates (median 3 SNPs versus 16 SNPs; P < 0.001). We further identified four clusters with German patients from same centers clustering with less than 25 SNPs distance (range 3 to 18 SNPs) but did not find any hint for in-hospital person-to-person transmission. This is the largest study investigating phylogenetic relations of M. abscessus isolates in Germany. We identified representatives of all reported DCCs but evidence for nosocomial transmission remained inconclusive. Thus, the occurrence of genetically closely related isolates of M. abscessus has to be interpreted with care, as a direct interhuman transmission cannot be directly deduced. IMPORTANCE Mycobacterium abscessus is a major respiratory pathogen in cystic fibrosis (CF) patients. Recently it has been shown that dominant global clonal complexes (DCCs) have spread worldwide among CF patients. This study investigated the epidemiological situation of M. abscessus among CF patients in Germany by performing whole-genome sequencing (WGS) of a set of 154 M. abscessus from 123 German patients treated in 14 CF centers. This is the largest study investigating the phylogenetic relationship of M. abscessus CF isolates in Germany.
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spelling doaj.art-6738412af9304c97bcbb8f38b2a682f12022-12-22T04:19:14ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-08-0110410.1128/spectrum.01714-22Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis PatientsNils Wetzstein0Margo Diricks1Thomas A. Kohl2Thomas A. Wichelhaus3Sönke Andres4Laura Paulowski5Carsten Schwarz6Astrid Lewin7Jan Kehrmann8Barbara C. Kahl9Karl Dichtl10Christian Hügel11Olaf Eickmeier12Christina Smaczny13Annika Schmidt14Stefan Zimmermann15Lutz Nährlich16Sylvia Hafkemeyer17Stefan Niemann18Florian P. Maurer19Michael Hogardt20Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyGerman Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyGerman Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyGerman Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyGerman Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyDivision of Cystic Fibrosis, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, GermanyUnit Mycotic and Parasitic Agents and Mycobacteria, Robert Koch Institute, Berlin, GermanyInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Münster, Münster, GermanyMax von Pettenkofer Institut, Institute of Medical Microbiology and Hygiene, Medizinische Fakultät, Ludwig-Maximilians-Universität, Munich, GermanyDepartment of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDivision for Allergy, Pneumology and Cystic Fibrosis, Department for Children and Adolescence, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Respiratory Medicine and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyInterfaculty Institute of Microbiology and Infection Medicine Tübingen, Insitute for Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, GermanyDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Pediatrics, Justus-Liebig-University Giessen, Giessen, GermanyMukoviszidose Institut, gemeinnützige Gesellschaft für Forschung und Therapieentwicklung mbH, Bonn, GermanyGerman Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyGerman Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyABSTRACT Infections due to Mycobacterium abscessus are a major cause of mortality and morbidity in cystic fibrosis (CF) patients. Furthermore, M. abscessus has been suspected to be involved in person-to-person transmissions. In 2016, dominant global clonal complexes (DCCs) that occur worldwide among CF patients have been described. To elucidate the epidemiological situation of M. abscessus among CF patients in Germany and to put these data into a global context, we performed whole-genome sequencing of a set of 154 M. abscessus isolates from 123 German patients treated in 14 CF centers. We used MTBseq pipeline to identify clusters of closely related isolates and correlate those with global findings. Genotypic drug susceptibility for macrolides and aminoglycosides was assessed by characterization of the erm(41), rrl, and rrs genes. By this approach, we could identify representatives of all major DCCs (Absc 1, Absc 2, and Mass 1) in our cohort. Intrapersonal isolates showed higher genetic relatedness than interpersonal isolates (median 3 SNPs versus 16 SNPs; P < 0.001). We further identified four clusters with German patients from same centers clustering with less than 25 SNPs distance (range 3 to 18 SNPs) but did not find any hint for in-hospital person-to-person transmission. This is the largest study investigating phylogenetic relations of M. abscessus isolates in Germany. We identified representatives of all reported DCCs but evidence for nosocomial transmission remained inconclusive. Thus, the occurrence of genetically closely related isolates of M. abscessus has to be interpreted with care, as a direct interhuman transmission cannot be directly deduced. IMPORTANCE Mycobacterium abscessus is a major respiratory pathogen in cystic fibrosis (CF) patients. Recently it has been shown that dominant global clonal complexes (DCCs) have spread worldwide among CF patients. This study investigated the epidemiological situation of M. abscessus among CF patients in Germany by performing whole-genome sequencing (WGS) of a set of 154 M. abscessus from 123 German patients treated in 14 CF centers. This is the largest study investigating the phylogenetic relationship of M. abscessus CF isolates in Germany.https://journals.asm.org/doi/10.1128/spectrum.01714-22Mycobacterium abscessuscystic fibrosiswhole-genome sequencingdominant circulating cloneshospital transmissionGerman CF registry
spellingShingle Nils Wetzstein
Margo Diricks
Thomas A. Kohl
Thomas A. Wichelhaus
Sönke Andres
Laura Paulowski
Carsten Schwarz
Astrid Lewin
Jan Kehrmann
Barbara C. Kahl
Karl Dichtl
Christian Hügel
Olaf Eickmeier
Christina Smaczny
Annika Schmidt
Stefan Zimmermann
Lutz Nährlich
Sylvia Hafkemeyer
Stefan Niemann
Florian P. Maurer
Michael Hogardt
Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients
Microbiology Spectrum
Mycobacterium abscessus
cystic fibrosis
whole-genome sequencing
dominant circulating clones
hospital transmission
German CF registry
title Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients
title_full Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients
title_fullStr Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients
title_full_unstemmed Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients
title_short Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients
title_sort molecular epidemiology of mycobacterium abscessus isolates recovered from german cystic fibrosis patients
topic Mycobacterium abscessus
cystic fibrosis
whole-genome sequencing
dominant circulating clones
hospital transmission
German CF registry
url https://journals.asm.org/doi/10.1128/spectrum.01714-22
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